The overall research aim of the Amazonian International Center of Excellence in Malaria Research is to organize a comprehensive approach to understanding the biological features of Amazonian malaria towards the ultimate goal of regional control and elimination of Plasmodium falciparum and P. vivax. While in the past the Amazonian ICEMR focused primarily on P. vivax because of its greater impact in the region, given recent developments in both Brazil and Peru, P. falciparum will also be a focus of our work. At the national level in Brazil, the national malaria control program has made P. falciparum a primary focus of elimination efforts, as P. falciparum malaria remains highly prevalent in the Juru Valley in western Brazilian Amazonia. In Peru, after the cessation of Global Fund-supported malaria control efforts in 2010, P. falciparum has reemerged as an important public health threat. The Amazonian ICEMR's recent meetings with the Loreto Ministry of Health witnessed the high level of concern about this re-emergence and the Ministry's interest in harnessing the Amazonian ICEMR's research strengths to addressing this emergent and timely issue. Overall, we anticipate that the lessons learned will contribute towards the audacious goal of global malaria eradication. The Amazonian ICEMR has 5 epidemiologically distinct malaria-endemic sites in Brazil and Peru. Project 1 focuses on malaria epidemiology and takes multidisciplinary approaches to study distinct transmission patterns in the Brazilian and Peruvian malaria-endemic sites using socio-demographic analysis, molecular epidemiology and genomics, and mathematical modeling to integrate all three ICEMR Projects, including Project 2, which focuses on vector ecology and transmission biology, and Project 3, which focuses on immunological mechanisms of asymptomatic parasitemia and clinical immunity, and to discover biosignatures of clinically immune (asymptomatic parasitemia) vs non-immune (acute, symptomatic malaria). Our long-term goal is to develop the scientific underpinnings of novel elimination strategies to be deployed in Amazonia, with broad generalizability to other malaria-endemic regions. This proposed Center therefore takes on a comprehensive approach to malaria research in the Peruvian and Brazilian Amazon, which will be used to inform Ministries of Health in Brazil and Peru, and officials of the Pan American Health Organization and the Amazonian Malaria Initiative, of new approaches to develop malaria elimination policies based on scientific data.